一个先天性厚甲症家系的遗传学研究  

Genetic study of a Chinese pedigree affected with pachyonychia congenita

作　　者：赵飞跃 邢碧颖 肖继芳[1] 赵秀丽[1] Zhao Feiyue;Xing Biying;Xiao Jifang;Zhao Xiuli(Department of Medical Genetics,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences-School of Basic Medicine,Peking Union Medical College,Beijing 100005,China;Beijing No.65 Middle School,Beijing 100006,China)

机构地区：[1]中国医学科学院基础医学研究所-北京协和医学院基础学院医学遗传学系,北京100005 [2]北京市第六十五中学,100006

出　　处：《中华医学遗传学杂志》2019年第10期985-988,共4页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划(2016YFC0905100).

摘　　要：目的在一个中国人先天性厚甲家系中进行致病基因突变鉴定.方法签署知情同意书后,抽取家系成员外周血,酚氯仿法提取基因组DNA;根据临床表现进行疾病分型,并确定候选致病基因;通过候选基因编码区聚合酶链反应扩增和DNA测序,在先证者中检测致病突变;通过突变区的PCR扩增和高分辨熔解曲线(high resolution melting,HRM)分析对家系所有成员进行基因型与表型共分离分析;通过微卫星标记单倍型分析确定家系的突变建立者.结果先证者KRT17基因第1外显子存在杂合错义突变c.275A>G(Asn92Ser);PCR-HRM分析证明该家系所有厚甲患者均携带该致病突变,而在家系和群体中的非厚甲个体中均未发现该突变;单倍型分析和测序结果表明先证者母亲为该家系c.275A>G(Asn92Ser)突变的建立者.结论我们在一个中国人先天厚甲家系中鉴定一个KRT17基因的热点突变c.275A>G(Asn92Ser),再次证实了该突变的致病性,为该家系患者的遗传咨询和产前诊断提供了依据.Objective To explore the genetic basis for a Chinese pedigree affected with pachyonychia congenita(PC).Methods With informed consent obtained,peripheral blood samples were taken from the pedigree.Genomic DNA was extracted with a phenol/chloroform method.Based on the clinical manifestation of the patients,candidate genes for PC were selected.Potential mutation was screened by PCR and Sanger sequencing.Suspected mutation was verified in other family members by PCR-high resolution melting(HRM)analysis.Haplotype analysis using microsatellite markers was also carried out to determine the founder of the mutation.Results A heterozygous c.275A>G(Asn92Ser)mutation was discovered in exon 1 of the KRT17 gene in the proband.PCR-HRM analysis showed that all affected members were heterozygous carriers of the mutation.The same mutation was found in none of the unaffected members.Haplotype analysis and sequencing indicated the mother of the proband to be the founder.Conclusion The c.275A>G(Asn92Ser)mutation of the KRT17 gene probably underlies the disease in this pedigree.Above finding has facilitated genetic counseling and prenatal diagnosis for this pedigree.

关 键 词：先天性厚甲 角蛋白17 基因突变 单倍型分析 高分辨熔解曲线 

分 类 号：R758[医药卫生—皮肤病学与性病学]